Among the many undesirable sequelae of ischemic stroke is the failure to recover motor skills. Current treatments for stroke are generally inadequate to prevent loss of motor skills which are resistant to recovery. Although it has been hypothesized that motor skills, among other deficits resulting from stroke, may be benefited from neurogenesis, leading, for example, to attempts to treat subjects using stem cells as sources of neuronal expansion (for example, Kokaia, Z., et al., Transl. Stroke Res. (2011) 2:272-278). Agents that enhanced neurogenesis in aged rats with cortical infarcts, however, did not effect behavioral recovery (Sun, X., et al., J. Mol. Neurosci. (2016) 58:233-242). Other negative effects include deficiencies in cognitive function.
A family of U.S. granted patents, represented by, for example, U.S. Pat. No. 8,362,262, discloses low molecular weight compounds that are capable of stimulating neuronal growth. These documents suggest that the compounds, which are shown to enhance neuronal growth, may be useful in the treatment of stroke; however, there is no disclosure that sustained subsequent treatment of stroke victims would be useful in the recovery of motor skills, of cognitive skills or enhancement of regeneration of neurons destroyed as secondary effects of stroke. Subsequently, it was found that certain 2-amino-substituted nicotinamides disclosed in these patents were useful in treating depression, in particular, major depressive disorder in humans as described in PCT publication WO2015/195567 and corresponding U.S. Pat. No. 9,572,807. Oral administration is disclosed. However, the motor skills deficits and cognitive deficits associated with stroke are not addressed by these documents.